Delivery methods, systems and components for use with hazardous pharmaceutical substances

ABSTRACT

A method of dispensing a hazardous pharmaceutical comprising the steps of: connecting a source of flushing fluid to a first port of a fluid delivery set; connecting a pressurizing unit of a powered injector system (including a powered injector and the pressurizing unit) to a second port of the fluid delivery set; purging air from the fluid delivery set; and, after purging air from the fluid delivery set, connecting a third port of the fluid delivery set to a source of the hazardous pharmaceutical. The fluid delivery set can, for example, include a valve system or assembly to control flow of fluid through the fluid delivery set. A system for delivery of a hazardous pharmaceutical includes: a syringe in operative connection with a powered injector; a protective container to enclose the syringe during operation thereof, the protective container being adapted to protect personnel from detrimental effects of the pharmaceutical; at least one source of flushing fluid; a fluid path adapted to connect to a patient; at least one source of the pharmaceutical; and a fluid delivery set including a valve assembly to which the syringe, the source of flushing fluid, the fluid path and the source of pharmaceutical are removably connectable. The valve assembly provides flow control through the fluid delivery set such that operator contact with the fluid delivery set is not required after connection of the source of pharmaceutical to the fluid delivery set.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application for patent claims the benefit of U.S.application Ser. No. 10/185,290, filed Jun. 27, 2002, which claimspriority to U.S. Provisional Application Serial No. 60/301,962, filedJun. 29, 2001. The contents of the aforementioned applications areincorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] The present invention relates to delivery methods, systems andcomponents thereof for use with hazardous or toxic pharmaceuticalsubstances, and especially to delivery and injection methods, systemsand components thereof for use with radiopharmaceutical substances.

[0003] As used herein, the term “pharmaceutical” refers to any substanceto be injected or otherwise delivered into the body (either human oranimal) in a medical procedure and includes, but is not limited,substances used in imaging procedures (for example, contrast media) andtherapeutic substances. A number of such pharmaceutical substances posea danger to both the patient and the personnel administering thesubstance if not handled and/or injected properly. Examples of hazardouspharmaceuticals include, but are not limited to, radiopharmaceuticals,biological pharmaceuticals, chemotherapeutic pharmaceuticals and genetherapeutic pharmaceuticals.

[0004] Examples of use of a radiopharmaceutical include positronemission tomography (PET) and single-photon emission computerizedtomography (SPECT), which are noninvasive, three-dimensional, imagingprocedures that provide information regarding physiological andbiochemical processes in patients. The first step in producing PETimages or SPECT images of, for example, the brain or another organ, isto inject the patient with a dose of the radiopharmaceutical. Theradiopharmaceutical is generally a radioactive substance that can beabsorbed by certain cells in the brain or other organ, concentrating itthere. For example, fluorodeoxyglucose (FDG) is a normal molecule ofglucose, the basic energy fuel of cells, to which is attached aradionuclide or radioactive fluor. The radionuclide is produced in acyclotron equipped with a unit to synthesize the FDG molecule.

[0005] Cells (for example, in the brain), which are more active in agiven period of time after an injection of FDG, will absorb more FDGbecause they have a higher metabolism and require more energy. Theradionuclide in the FDG molecule suffers a radioactive decay, emitting apositron. When a positron collides with an electron, an annihilationoccurs, liberating a burst of energy in the form of two beams of gammarays in opposite directions. The PET scanner detects the emitted gammarays to compile a three dimensional image.

[0006] In that regard, after injecting the radiopharmaceutical, thepatient is typically placed on a moveable bed that slides by remotecontrol into a circular opening of the scanner referred to as thegantry. Positioned around the opening, and inside the gantry, areseveral rings of radiation detectors. Each detector emits a brief pulseof light every time it is struck with a gamma ray coming from theradionuclide within the patient's body. The pulse of light is amplified,by a photomultiplier, and the information is sent to the computer thatcontrols the apparatus.

[0007] The timing of injection is very important. After the generationof the radiopharmaceutical, a countdown begins. After a certain time,which is a function of the half-life of the radionuclide, the radiationlevel of the radiopharmaceutical dose falls exactly to a level requiredfor the measurement by the scanner. In current practice, the radiationlevel of the radiopharmaceutical volume or dose is typically measuredusing a dose calibrator. Using the half-life of the radionuclide, thetime that the dose should be injected to provide the desired level ofradioactivity to the body is calculated. When that time is reached, theradiopharmaceutical dose is injected using a manually operated syringe.

[0008] Most PET radionuclides have short half-lives. Under properinjection procedures, these radionuclides can be safely administered toa patient in the form a labeled substrate, ligand, drug, antibody,neurotransmitter or other compound normally processed or used by thebody (for example, glucose) that acts as a tracer of specificphysiological and biological processes.

[0009] Excessive radiation to technologists and other personnel workingin the scanner room can pose a significant risk, however. Although thehalf-life of the radiopharmaceutical is rather short and the applieddosages are themselves not harmful to the patient, administeringpersonnel are exposed each time they work with the radiopharmaceuticalsand other contaminated materials under current procedures. Constant andrepeated exposure over an extended period of time can be harmful.

[0010] A number of techniques used to reduce exposure include minimizingthe time of exposure of personnel, maintaining distance betweenpersonnel and the source of radiation and shielding personnel from thesource of radiation. In general, the radiopharmaceuticals are typicallydelivered to a nuclear medicine facility from another facility equippedwith a cyclotron in, for example, a lead-shielded container. Often, theradiopharmaceutical is manually drawn from such containers into ashielded syringe. See, for example, U.S. Pat. No. 5,927,351 disclosing adrawing station for handling radiopharmaceuticals for use in syringes.Remote injection mechanisms can also be used to maintain distancebetween the operator and the radiopharmaceutical. See, for example, U.S.Pat. No. 5,514,071, disclosing an apparatus for remotely administeringradioactive material from a lead encapsulated syringe.

[0011] In one procedure, the radiopharmaceutical is injected into tubingthat is coiled within a lead container. Typically, the shielded syringeused to inject the radiopharmaceutical is disconnected and replaced by alarger syringe, filled in most cases with saline, for injection into thebody and flush. By emptying the second syringe, the radiopharmaceuticalis flushed through the shielded, coiled tubing in the container andinjected into the person to be scanned. An excess volume of salinesupplies a flushing function.

[0012] Although substantial effort is made to reduce exposure ofadministering and other personnel to harmful radiation, some exposure isexperienced under current procedures. Being in the injection room longerthan necessary is thus to be avoided. Moreover, the cumulative radiationexposure resulting from multiple injection procedures must be closelymonitored to avoid overexposure. Indeed, personnel that administerradiopharmaceuticals are typically periodically rotated out of suchduties to reduce the risk of overexposure.

[0013] In addition to the difficulties introduced by the hazardousnature of radiopharmaceuticals, the short half-lives of suchradiopharmaceuticals further complicate the administration of a properdosage to a patient. As discussed above, initial calibration ofradioactivity is often made and the injection is then timed so that adose of the desired level of radioactivity to the body is delivered (ascalculated from the half-life of the radiopharmaceutical). See, forexample, U.S. Pat. No. 4,472,403 in which a motor driven syringe iscontrolled to inject a quantity of a radiopharmaceutical stored in thesyringe by calculating the injection quantity based upon the half-lifeof the radiopharmaceutical and the delay before injection.

[0014] Radiation detectors have also been placed upon syringe shieldsand in line with the radiopharmaceutical delivery system. For example,U.S. Pat. No. 4,401,108 discloses a syringe loading shield for useduring drawing, calibration and injection of radiopharmaceuticals. Thesyringe shield includes a radiation detector for detecting andcalibrating the radioactive dosage of the radiopharmaceutical drawn intothe syringe. U.S. Pat. Nos. 4,562,829 and 4,585,009 disclosestrontium-rubidium infusion systems and a dosimetry system for usetherein. The infusion system includes a generator of thestrontium-rubidium radiopharmaceutical in fluid connection with syringefor supplying pressurized saline. Saline pumped through thestrontium-rubidium generator exits the generator either to the patientor to waste collection. Tubing in line between the generator and thepatient passes in front of a dosimetry probe to count the number ofdisintegrations that occur. As the flow rate through the tubing isknown, it is possible to measure the total activity delivered to thepatient (for example, in milliCuries). Likewise, radiation measurementshave been made upon blood flowing through the patient. For example, U.S.Pat. No. 4,409,966 discloses shunting of blood flow from a patientthrough a radiation detector.

[0015] The danger to administering personnel and other difficulties thatarise from the nature of hazardous pharmaceuticals such asradiopharmaceuticals often affect the quality and safety of theinjection procedure. For example, given the care that must be taken toprevent radiation overexposure (including limiting the duration ofinjection procedures), the concern with properly timing an injection andthe need to prevent the creation of radioactive wastes, it is oftendifficult to properly eliminate air from all fluid paths before aninjection begins.

[0016] It is thus very desirable to develop devices, systems and methodsthrough which toxic or hazardous pharmaceuticals (for example,radiopharmaceuticals) can be administered in controlled manner toenhance their effectiveness and patient safety, while reducing exposureof administering personnel to such hazardous pharmaceuticals.

SUMMARY OF THE INVENTION

[0017] In one aspect, the present invention provides a method ofinjecting a hazardous pharmaceutical comprising the steps of: connectinga source of flushing fluid to a first port of a fluid delivery set;connecting a pressurizing unit of a powered injector system (including apowered injector and the pressurizing unit) to a second port of thefluid delivery set; purging air from the fluid delivery set; and, afterpurging air from the fluid delivery set, connecting a third port of thefluid delivery set to a source of the hazardous pharmaceutical. Thefluid delivery set can, for example, include a valve system or assemblyto control flow of fluid through the fluid delivery set. The ports ofthe fluid delivery set can, for example, include luer connectors asknown in the medical arts to form a removable, secure and generallysealed connection.

[0018] The method preferably further includes the steps of (i) removablyconnecting a disposable fluid path that is connectable (via, forexample, a catheter) to a patient to the fluid delivery set and (ii)purging air from the disposable fluid path before connecting the fluiddelivery set to the source of hazardous pharmaceutical.

[0019] By removing air from the fluid delivery set and the patient fluidpath before any connection is made to the source of hazardouspharmaceutical, exposure of administering personnel to the hazardouspharmaceutical to that point is eliminated. Connecting the fluiddelivery set to the source of pharmaceutical can be automated orotherwise accomplished remotely (for example, with use of an extendingor robotic arm as known in the machine and robotic arts) to preventexposure during that connection.

[0020] The pressurizing unit can, for example, be a syringe in operativeconnection with the powered injector. In the case that the pressurizingunit is a syringe, the method can further include the steps of drawingthe hazardous pharmaceutical into the syringe and injecting thehazardous pharmaceutical through the fluid delivery set and thedisposable fluid path. Using a powered injector having a control unitremoved in distance or shielded from the position of the syringe, fluiddelivery set and fluid path prevents exposure of operating/administeringpersonnel to the hazardous pharmaceutical. The method preferably furtherincludes the step of flushing the fluid delivery set and the disposablefluid path after injection using the flushing fluid (for example, salineand/or another biologically acceptable flushing agent). A poweredinjector can also be used with a saline syringe in a similar manner asdescribed above to limit exposure of operating personnel to thehazardous pharmaceutical.

[0021] In the case that the hazardous pharmaceutical is aradiopharmaceutical, the method can further include the step ofmeasuring the level or dosage of radioactivity of theradiopharmaceutical injected. Preferably, the level of radioactivity ordosage is measured very near in time or simultaneously with delivery ofthe radiopharmaceutical to provide an accurate measurement of the dosagedelivered. For example, the level of radioactivity can be measured bypositioning the syringe within a dose calibrator. The level ofradioactivity can also be measured by placing a radioactivity detectorin operative connection with a line through which theradiopharmaceutical is dispensed or delivered.

[0022] In another aspect, the present invention provides a system fordelivery of a hazardous pharmaceutical including: a syringe in operativeconnection with a powered injector and a protective container to enclosethe syringe during operation thereof. The protective container isconstructed or adapted to protect personnel from detrimental effects ofthe pharmaceutical. The system preferably also includes at least onesource of flushing fluid; a fluid path adapted to connect to a patient;at least one source of the pharmaceutical; and a fluid delivery set. Thefluid delivery set preferably includes a valve assembly to which thesyringe, the source of flushing fluid, the fluid path and the source ofpharmaceutical are removably connectable.

[0023] The valve assembly preferably provides flow control through thefluid delivery set such that operator contact with the fluid deliveryset is not required after connection of the source of pharmaceutical tothe fluid delivery set. The valve assembly also preferably provides flowcontrol through the fluid delivery set such that the entire fluiddelivery set can be purged of air with the syringe and the source offlushing fluid in fluid connection with the valve assembly before thesource of pharmaceutical is connected to the fluid delivery set. In oneembodiment, the valve assembly includes a bypass line in continuousfluid connection between the source of flushing fluid and the fluidpath.

[0024] In the case that the pharmaceutical is a radiopharmaceutical, theprotective container can, for example, be a component of a dosecalibrator adapted to measure the level of radioactivity of thepharmaceutical within the syringe. In one embodiment, the syringe isconnected to the powered injector via an extending adapter thatpreferably extends from the powered injector when connected thereto toposition the syringe within the protective container.

[0025] The adapter can, for example, include an injector attachmentmember to attach the adapter to a powered injector and a plungerextension fixed in position relative to a powered injector. The plungerextension preferably has a plunger attachment member to attach to aplunger of the syringe. In one embodiment, the adapter also includes asyringe carriage slidably attached to the adapter. The syringe carriageincludes a syringe attachment member to removably attach a syringethereto so that a barrel of a syringe can be moved relative to a plungerthereof to control fluid flow into and out of a syringe.

[0026] The above embodiment of an adapter facilitates orientation of thesyringe tip or exit of the syringe directed toward the powered injectorwhen the syringe is attached to the syringe attachment member. Thisorientation can facilitate purging of air from the syringe when thesyringe is placed within, for example, a dose calibrator positionedbelow the injector. In that regard, lead-shielded dose calibrators areoften relatively large and heavy and thus positioned most easily nearthe floor. Moreover, this relative positioning of the injector and dosecalibrator assists in limiting exposure of operating/administeringpersonnel by directing any waves of radiation escaping from the dosecalibrator upward to the ceiling of the room. Moving the syringe barrelrelative to the syringe plunger in the manner described in the aboveembodiment facilitates use of commercially available injectors andsyringes for use therewith by eliminating the need to change/recalibratethe direction and distance the injector drive member must advance orretract to complete a desired operation.

[0027] In another aspect, the present invention provides a method ofusing a powered injector system to inject a radiopharmaceutical into abody. The method includes the steps of: attaching an extending adapterto the front end of the powered injector; the adapter including aninjector attachment to place the adapter in operative connection withthe powered injector, the adapter also including a syringe attachment toattach a syringe to the adapter to place the syringe in operativeconnection with the powered injector; and extending the adapter into aradiation shield. As discussed above, the radiation shield can form partof a dose calibrator to measure the radioactivity of radiopharmaceuticalwithin the syringe. In one embodiment, the exit of the syringe isoriented upward relative to the opposite end of the syringe when thesyringe is positioned within the dose calibrator to facilitate purgingof air from the syringe. As discussed above, the opening through whichthe syringe passed to enter the dose calibrator is preferably orientedin a direction (for example, upward toward the ceiling) to decrease thelikelihood of exposure of personnel to any radiation waves exiting thedose calibrator during use thereof.

[0028] In a further aspect, the present invention provides an adapterfor use with a powered injector to attach a syringe to the poweredinjector including: an injector attachment member to attach the adapterto a powered injector and a syringe attachment member spaced from theinjector attachment member by a sufficient distance to position asyringe attached to the syringe attachment member within a radiationdose calibrator. Preferably, the adapter facilitates use of commerciallyavailable injector systems with commercially available dose calibratorswithout the requirement of substantial and/or expensive modificationthereto.

[0029] In another aspect, the present invention provides an adapter foruse with a powered injector to attach a syringe to the powered injectorincluding an injector attachment member to attach the adapter to apowered injector and a plunger extension fixed in position relative to apowered injector. The plunger extension has a plunger attachment memberto attach to a plunger of the syringe. The adapter further includes asyringe carriage slidably attached to the adapter and including asyringe attachment member to removably attach a syringe thereto so thata barrel of the syringe can be moved relative to a plunger thereof tocontrol fluid flow into and out of the syringe. As discussed above, thesyringe can be oriented with a syringe tip thereof directed toward thepowered injector when attached to the syringe attachment member.

[0030] In another aspect, an adapter includes an attachment member toremovably attach the adapter to a powered injector and a syringecarriage slidably attached to the attachment member. The syringecarriage includes a syringe attachment member to which a syringe can beremovably attached. The adapter further includes an end member attacheda fixed distance from the attachment member. The end member has aplunger extension attached to the end member and extending toward theinjector. The plunger extension includes a plunger attachment member onan end thereof opposite the end attached to the end member. The syringecarriage is adapted to move a barrel of the syringe relative to aplunger of the syringe when a syringe is attached to the syringeattachment member and a plunger thereof is attached to the plungerextension member.

[0031] In another aspect, the present invention provides a shield foruse with a radiopharmaceutical including a housing that is impenetrableby radioactive energy from the radiopharmaceutical. The shield alsoincludes at least one opening in the housing through which an articlecontaining the radiopharmaceutical, which is positioned within thehousing, can be viewed. The opening is in visual alignment with areflective surface in which a viewer can view a reflection of thearticle. The opening is positioned within the housing such that there isno direct line between the viewer and the article that is not shieldedby a portion of the housing. Because radiation energy fromradiopharmaceuticals travels in straight lines, the viewer is shieldedfrom exposure to radiation.

[0032] In a further aspect, the present invention provides a method ofinjecting a radiopharmaceutical into a body. The method includes thesteps of: positioning a pressurizing unit or device containing a firstvolume of the radiopharmaceutical within a dose calibrating unit adaptedto measure the level of radioactivity of the radiopharmaceutical; andinjecting a second volume of the radiopharmaceutical. The second volumeis determined through measurement by the dose calibrating unit toprovide a desired level of radioactivity. The second volume can, forexample, be less than the first volume. In one embodiment, thepressurizing chamber is a syringe in fluid connection with a poweredinjector.

[0033] In another aspect, the present invention provides a kit forinjecting a hazardous pharmaceutical into a body including: a fluid pathadapted to connect to a patient; and a fluid delivery set. The fluiddelivery set includes a valve assembly to which a pressurizing unit, asource of flushing fluid, the fluid path and a source of thepharmaceutical are removably connectable. The valve assembly providesflow control through the fluid delivery set such that operator contactwith the fluid delivery set is not required after connection of thesource of pharmaceutical to the fluid delivery set. The valve assemblyalso preferably provides flow control through the fluid delivery setsuch that the entire fluid delivery set can be purged of air with thesyringe and the source of saline in fluid connection with the valveassembly before the source of pharmaceutical is connected to the fluiddelivery set.

[0034] In still a further aspect, the present invention provides amethod of injecting a radiopharmaceutical into a patient. The methodcomprises the steps of: connecting a powered pressurizing device that iscontrolled without intimate or close contact by an operator (forexample, remotely controlled, automated or preprogrammed so that theoperator is not within a radiation field of a dangerous level) to avalve assembly of a fluid delivery set; connecting at least one sourceof a flushing fluid to the valve assembly; connecting a patient fluidpath to the valve assembly, the patient fluid path terminating in apatient connector; connecting a source of a ready-made (that is,prepared earlier—for example, in an offsite cyclotron)radiopharmaceutical to the valve assembly; and controlling the valveassembly at least during injection of the hazardous pharmaceutical suchthat operator presence in the vicinity of the radiopharmaceutical is notrequired. In general, a dose to an individual decreases with the squareof the distance from the radiation source. Thus, close operator contactwith the pressurizing device, fluid delivery set and other components ofthe fluid delivery system is not required when the radiopharmaceuticalis present in the fluid delivery system. Moreover, shielding asdescribed above can also be used to prevent exposure. The valve assemblycan also be controlled without intimate contact by an operator (forexample, remotely controlled, automated or preprogrammed).

[0035] In general, the present invention provides for administration ordelivery of a toxic or hazardous pharmaceuticals (for example,radiopharmaceuticals) in controlled manner to enhance the effectivenessof the pharmaceutical and to enhance patient safety (as compared tocurrent procedures and equipment for delivering such pharmaceuticals),while reducing exposure of administering personnel to the hazardouspharmaceuticals. In general, commercially available injector systems arereadily adaptable for use in the present invention without substantialor expensive modification.

BRIEF DESCRIPTION OF THE DRAWINGS

[0036]FIG. 1A illustrates a schematic representation of an embodiment ofa system of the present invention.

[0037]FIG. 1B illustrates a top cross-sectional view of an embodiment ofa shielded container for a fluid delivery set of the present invention.

[0038]FIG. 1C illustrates a side cross-sectional view of anotherembodiment of a shielded container for a fluid delivery set of thepresent invention.

[0039]FIG. 2A illustrates a perspective view of an embodiment of aninjector and a syringe adapter of the system of the present invention.

[0040]FIG. 2B illustrates a perspective view of injector control unitsused in connection with the injector of the present invention.

[0041]FIG. 3 illustrates a perspective view of the system of the presentinvention in which the injector head and syringe adapter have beenlowered so that the syringe is positioned within the dose calibrationunit.

[0042]FIG. 4A illustrates a perspective view of the adapter of FIG. 2Adetached from the injector with the syringe attached thereto.

[0043]FIG. 4B illustrates a perspective view of the adapter of FIG. 2Adetached from the injector with the syringe detached therefrom.

[0044]FIG. 4C illustrates a side cross-sectional view a portion of thesystem of FIGS. 1 through 4B.

[0045]FIG. 5A illustrates a side cross-sectional view of an embodimentof the present invention in which dose calibration is provided byplacing a pressurizing device and a source of radiopharmaceutical withina shielded dose calibrator.

[0046]FIG. 5B illustrates a side cross-sectional view of an embodimentof the present invention in which dose calibration is provided byplacing a source of radiopharmaceutical within a shielded dosecalibrator.

[0047]FIG. 5C illustrates a side cross-sectional view of an embodimentof the present invention in which dose calibration is provided byplacing a radiation detector in line between a pressurizing device and asource of radiopharmaceutical within a shielded dose calibrator.

[0048]FIG. 5D illustrates a side cross-sectional view of an embodimentof the present invention in which dose calibration is provided byplacing a radiation detector in line with the exit line of apressurizing device.

DETAILED DESCRIPTION OF THE INVENTION

[0049] As illustrated in FIG. 1A, in one embodiment of the presentinvention, a system 10 includes a fluid delivery set or system 15including a valve system 16 that provides a fluid connection for asaline source 20 (for example, a syringe), a source 40 of apharmaceutical to be injected into a patient, a pressurizing chamber orunit for the pharmaceutical (for example, a syringe 60 in fluidconnection with a powered injector 70 in the embodiment of FIG. 1) and afluid path set 80 that is connectable to the patient (via, for example,tubing terminating in a catheter 100). In general, the fluid deliveryset 15, valve system 16 and other elements of the present inventionenable purging of air from the system, filling of syringe 60 with thepharmaceutical, delivery of the pharmaceutical (for example, injectingthe pharmaceutical into the patient) via syringe 60, and providing asaline flush, while minimizing or eliminating exposure of administeringor operating personnel to the detrimental effects of the pharmaceuticaland minimizing or eliminating creation of contaminated waste. Moreover,fluid delivery set 15 and other elements of the present invention alsofacilitate safe delivery of the pharmaceutical to multiple destinations(for example, injection into a series patients).

[0050] In the embodiment of FIG. 1, valve system 16 includes a three-waystopcock 30 including a first port 32 that is in fluid connection withsaline syringe 20. A second port 34 of stopcock 30 is in fluidconnection with source 40 of a toxic or hazardous pharmaceutical (forexample, a radiopharmaceutical). Source 40 of the pharmaceutical ispreferably enclosed within a container 44 that is designed to reduce therisk of contamination of personnel administering the pharmaceutical. Forexample, in the case of a radiopharmaceutical, the container can befabricated from lead or tungsten to substantially prevent exposure ofsuch personnel to undesirably high levels of radiation.

[0051] A third port 36 of stopcock 30 is in fluid connection with, forexample, a dual check valve 50. The flow through stopcock 30 iscontrolled via control 38. A first port 52 of dual check valve 50 is influid connection with syringe 60 that is preferably in operativeconnection with powered injector 70. A second port 54 of dual checkvalve 50 is preferably in fluid connection with patient fluid path set80 that includes, for example, flexible tubing 90 connected to catheter100. Preferably, patient fluid path set 80 is disposable on a perpatient basis to reduce the likelihood of cross-contamination whensystem 10 is used for injection of fluids into multiple patients.Patient fluid path set 80 is preferably in fluid connection with secondport 54 of dual check valve 50 via a one-way check valve 110 to furtherreduce the likelihood of cross-contamination.

[0052] Preferably, saline source 20 is also in fluid connection withfluid path set 80 via bypass tubing or conduit 120 of valve system 16 toprovide, for example, flush and KVO (keep vein open) functions on demandwithout having to adjust control 38 of valve system 16. In theembodiment of FIG. 1, a tee 130 is positioned between saline source 20and stopcock 30. A side port 132 of tee 130 is in fluid connection withbypass tubing 120. Bypass tubing 120 is preferably in fluid connectionwith check valve 110 (and thereby with fluid path set 80) via a one-waycheck valve 140.

[0053] In injection procedures and other fluid delivery operations inwhich non-hazardous pharmaceuticals are delivered, purging air from theentire fluid path (including, the fluid path between a source of thepharmaceutical and the delivery point) typically includes the forcing anamount of the pharmaceutical through the fluid path to, for example, awaste receptor before beginning the procedure (for example, beforeinsertion of a catheter into the patient). However, in the case of ahazardous pharmaceutical such as a radiopharmaceutical, it is verydesirable to minimize or eliminate the creation of waste pharmaceutical.Moreover, as discussed above, it is also preferable in the case of ahazardous pharmaceutical to minimize exposure of administering personnelto the pharmaceutical. The present invention thus preferably enablespurging of air from the entirety of fluid delivery set 15 (andpreferably, also from patient fluid path set 80) before connection offluid delivery set 15 to pharmaceutical source 40. In this manner,exposure of administering personnel to hazardous materials duringpurging is eliminated and no hazardous waste is generated.

[0054] After connecting fluid delivery set 15, which is fluid filled andpurged of air, to pharmaceutical source 40, air can be introduced intofluid delivery system 10 from pharmaceutical source 40. Thus,precautions are preferably taken as known in the art to reduce thelikelihood of introduction of air into system 10 from pharmaceuticalsource 40. Moreover, a bubble detector 150 can be placed incommunication with line 46 to detect if air is drawn from pharmaceuticalsource 40. Examples of a bubble detector suitable for use in the presentinvention include the BDF/BDP series ultrasonic air bubble detectorsavailable from Introtek of Edgewood, N.Y.

[0055] In the case that it is desirable to purge system 10 (for example,in the case that air is found in one of the fluid path lines), a wastecontainer 161 (which is preferably shielded) is preferably provided. Inthe embodiment of FIG. 1A, waste container 161 is in fluid connectionwith a control valve 171 (similar in operation to control valve 30)which is in line just before check valve 110. Control valve 171 can becontrolled remotely or automated to reduce likelihood of exposure ofoperating personnel to the toxic pharmaceutical. It is also possible,for example, to provide valve 50 with control in a manner known to thoseskilled in art such that fluid can be purged back to source 40. Ingeneral, system 10 is purged using syringe 60 and/or saline source 20 asdescribed below.

[0056] During operation of system 10, saline syringe 20 (which can be ahand syringe or a syringe powered by an injector 24) is first filledwith saline. Saline syringe 20 is then connected to valve system 16 offluid delivery set 15 via first port 32 on three-way stopcock 30. Salinesyringe 20 is preferably used to purge air from system 10. Salinesyringe 20 also provides a flush to patient fluid path set 80 afterinjection of pharmaceutical(s) to ensure that substantially all thepharmaceutical is injected into the patient and to ensure that verylittle if any of the toxic or hazardous pharmaceutical remains, forexample, within fluid path set 80.

[0057] Syringe 60 is attached to injector 70. In the case of injectionof a radiopharmaceutical, at least syringe 60 of injector 70 ispreferably enclosed within a shielded container during an injectionprocedure. In one embodiment, the shielded container is a radiation dosecalibration unit 200 as discussed in further detail below. Air is firstpreferably expelled from syringe 60 by advancing plunger 62 of syringe60 toward syringe tip 64. Syringe 60 is then connected to dual checkvalve 50 of valve system 16 via first port 52. Patient fluid path set 80is connected to valve system 16 via one-way check valve 110.

[0058] Control 38 is adjusted to place saline syringe 20 in fluidconnection with tubing 46. Tubing 46 can, for example, terminate in aspike 48 or other connection member to cooperate with a septum 45 onsource 40 (for example, a bottle) as known in the art. A small volume ofsaline is injected or expelled from saline syringe 20 to purge air fromtubing 46 and spike 48. Control 38 is then adjusted to place salinesyringe 20 in fluid connection with dual check valve 50. A small volumeof saline is expelled to purge flush bypass line 120 of air. Dual checkvalve 50 provides sufficient resistance to flow such that salineexpelled from saline syringe 20 passes through bypass line 120 ratherthan through dual check valve 50.

[0059] Injector 70 is used to retract plunger 62 to draw saline fromsaline syringe 20. Injector 70 is then used to expel air in line betweensyringe 60 and catheter 100 by expelling (via advancement of plunger 62)the saline therefrom. At this point, all lines of system 10 are free ofair and filled with saline. Syringe 60 is substantially empty except fora small amount of saline not expelled.

[0060] At this point, injector syringe 60 is preferably positionedwithin dose calibrating unit 200 or other radiation containment devicein the case of injection of a radiopharmaceutical. Container 44 isopened and pharmaceutical source 40 is spiked to place source 40 influid connection with valve system 16. Spiking of pharmaceutical source40 can be done automatically, remotely or robotically to reduce orprevent exposure of operating personnel. The patient is then connectedto patient fluid path set 80 via catheter 100. System 10 is now readyfor an injection. The pharmaceutical is drawn into syringe 60 byretraction of plunger 62 relative to syringe tip 64 and then injectedinto the patient by advancement of plunger 62 relative to syringe tip64. Saline is then expelled from saline syringe 20, passing throughbypass line 120, to flush the pharmaceutical from patient fluid path set80. All of these functions are accomplished with little on no exposureof the operator or administering personnel to radiation.

[0061] In that regard, all adjustments of control 38 were made beforethe radiopharmaceutical was drawn into fluid delivery set 15. Control 38can also be adjusted remotely or automatically (for example, viaelectronic/computer control) in, for example, cases when somepharmaceutical is within fluid delivery set 15 (for example, in a secondor subsequent procedure in a case in which fluid delivery set 15 is usedfor multiple deliveries/injections) to prevent exposure of administeringpersonnel. Other types of valve systems or assemblies, for example, amanifold system, can be used to affect the control of valve assembly 16.

[0062] Fluid delivery set 15 is preferably disposable after one or moreuses to, for example, reduce the risk of cross-contamination betweenpatients. Fluid delivery set 15, including valve system 16, and/or othercomponents of system 10 can be placed within a protective containmentunit 18 during use thereof to further shield personnel from radiationthat may emanate from, for example, valve system 16. FIG. 1B illustratesone embodiment of protective containment unit or shielded container 18for fluid delivery set 15 of the present invention. In general,radioactive rays emanate in straight lines from a radiation source.Containment unit 18 provides a view of fluid delivery set 15 withoutproviding a straight line of sight between the viewer and fluid deliveryset 15. In that regard, it is often desirable for administeringpersonnel to have a view of tubing in a fluid path to, for example,provide visual assurance of the absence of air bubbles. Containment unit18 includes a shielded housing 160 having a view port 162. Radioactiverays cannot escape through view port 162, as there is no line of sight(that is, unobstructed line) between view port 162 and fluid deliveryset 15. Containment unit 18 includes a mirrored surface 164 to provide aview of fluid delivery set 15. FIG. 1C illustrates another embodiment ofa containment unit 18a in which a view of fluid delivery set 15 isprovided by mirrored surface 174, which is in alignment with fluiddelivery set 15 via view port 172. One or more additional mirroredsurfaces 176 can be provided to give further views of fluid delivery set15.

[0063] In each of containment units 18 and 18 a, one or more mirroredsurfaces are used to provide a view of fluid delivery set 15 withoutcreating an unshielded direct line between the viewer and the fluiddelivery set 15 (or other radioactive source). There is no need toprovide a transparent shield (for example, lead shielded glass) overview ports 162 or 172 because the lack of an unshielded direct line ofsight between the viewer and fluid delivery set 15 prevents exposure toradiation. Elimination of leaded glass can be advantageous as such glassis often expensive and heavy and can sometimes diminish or degrade aview.

[0064] In the case of injection of a radiopharmaceutical, positioning apressurizing unit or chamber such as syringe 60 within dose calibratingunit 200 such as the Capintec CRC-15PET dose calibrator available fromCapintec, Inc. of Ramsey, N.J., which measures the total radiation ofthe volume of radiopharmaceutical enclosed within the pressurizingchamber, shields administering personnel from radiation and enablesdelivery of a known volume of the radiopharmaceutical having a knownradiation level (as measured directly by dose calibrating unit 200). Theaccurate control of injection volume and flow rate provided by poweredinjector 70 enables automatic injection of a calculated volume of fluid(using for example processing unit 71 of injector 70) that will providethe level of radiation necessary, for example, for a PET or SPECT imagegiven the measured radiation of the total volume of radiopharmaceuticalcontained within syringe 60 provided by dose calibration unit 200. Thus,it is no longer necessary to calculate and wait for the precise momentin time when radioactive decay has brought the level of radiation of avolume of radiopharmaceutical to the desired level, thereby saving timeand reducing the complexity of the injection procedure.

[0065]FIG. 2-4C illustrate one embodiment of a setup for system 10 asdescribed above. In this embodiment, a PULSAR injector available fromMedrad, Inc. of Indianola, Pa. was used. Injection head 72 was separatedfrom control unit 74 as described in U.S. Provisional Patent ApplicationSerial No. 60/167,309, filed Nov. 24, 1999, U.S. patent application Ser.No. 09/721,427, filed Nov. 22, 2000 and U.S. patent application Ser. No.09/826,430, filed Apr. 3, 2001, all assigned to the assignee of thepresent invention. Injection head 72 is slidably positioned in generalalignment with an opening 204 in dose calibration unit 200 on agenerally vertical slide bar or stand 220 via a clamping extension 224.Injector 70 also includes a first remote control unit 76 forcommunicating data/instructions such as injection volume and flow rateinto control unit 74 remotely (via, for example, communication line 75).Further, injector 70 includes a second remote control unit 78 for remotemanual control of drive member 79 of injector 70. The function of firstremote control unit 76 and second control unit 78 can be combined. Oncurrently available PULSAR injectors, manual controls for drive member79 are positioned upon injector head 72. However, to prevent undesirableexposure to radiation in system 10 of the present invention, suchcontrols are preferably also positioned remotely from injector head 72.Saline source/syringe 20 can also be controlled via injector 70 througha second injector head (not shown) as described, for example, in U.S.Provisional Patent Application Serial No. 60/167,309, filed Nov. 24,1999, U.S. patent application Ser. No. 09/721,427, filed Nov. 22, 2000and U.S. patent application Ser. No. 09/826,430, filed Apr. 3, 2001.

[0066] In the embodiment of FIGS. 2A through 4C, system 10 is positionedupon a cabinet stand 300. Slide bar 220 extends generally verticallyfrom cabinet stand 300. Cabinet stand 300 includes a passage 310 formedtherein through which syringe 60 can pass to enter dose calibration unit200. Cabinet stand 300 also preferably includes a second passage 320through which pharmaceutical source 40 can pass to be deposited withincontainer 44. A cap 330 can be provided to seal container 44. In theembodiment of FIG. 2A through 4C, first passage 310 is preferablyoriented such that radiation emanating therefrom is directed generallyvertically toward the ceiling (or in another suitable direction) toreduce the likelihood that personnel within the room of the injectionprocedure will be exposed to such radiation.

[0067] Injector head 72 is oriented in a generally vertical, downwarddirection on slide bar 220 to position syringe 60 within dosecalibrating unit 200. To ensure that air is purged from a syringe,however, injector heads are typically positioned such that the exit, ortip, of the syringe is oriented upward during purging. As air is lessdense than other injection media and saline flushes, the air rises tothe syringe tip or exit and is readily purged by, for example, forcing asmall amount of fluid from the syringe. To enable a generally verticalorientation of syringe 60 with syringe tip 64 oriented upward in thepresent invention, a syringe adapter 400 was used.

[0068] Syringe adapter 400 attaches to injector 70 in preferably thesame manner as syringes are attached thereto. Attachment adapters can beused as known in the art to facilitate such attachment. Adapter 400 can,for example, be removably attached to injector 70 via flanges 412 on anattachment member 410 that cooperate with retaining slots in injector 70(not shown) as described in U.S. Pat. No. 5,383,858, assigned to theassignee of the present invention, the disclosure of which isincorporated herein by reference.

[0069] Adapter 400 includes a drive extension 420 that removablyconnects to drive member 79 of injector 70 via an attachment member 430that can, for example, include capture members that cooperate with adrive member flange 79′. Drive extension 420 attaches to a syringecarriage 440 at an upper plate member 442 of syringe carriage 440.Syringe carriage 440 is slidably disposed upon adapter 400 via slidebars 450 a and 450 b that extend from the rear surface of attachmentmember 410 to a fixed, lower base 460. Syringe carriage 440 includes asyringe attachment member 444 attached to a lower plate member 446 ofsyringe carriage 440. Upper plate member 442 and lower plate member 446are connected via connecting members 448 (for example, metal or plasticbars). Syringe attachment member 444 can include slots (not shown) thatcooperate with flanges 66 on a rear portion of syringe 60 to removablyattach syringe 60 to syringe carriage 440 as illustrated in FIGS. 4A and4C (as described, for example, in U.S. Pat. No. 5,383,858). Via syringecarriage 440, the barrel of syringe 60 is slidable in an upward anddownward direction on adapter 400.

[0070] Adapter 400 further includes a plunger extension 470 thatincludes a plunger attachment including, for example, a flange 474 thatcooperates with capture members 63 on the rear of plunger 62 toremovably connect plunger extension 470 to plunger 62. Adapters as knownin the art can facilitate connection of plunger extension 470 to variousplungers. Plunger extension 470 maintains plunger 62 in a fixed positionrelative to base 460 and injector head 72. By upward and downwardmovement of syringe carriage 440 (via injector drive member 79 and driveextension 420), the position of plunger 62 within syringe 60 is changed.For example, advancing drive member 79 causes the barrel of syringe 60to move downward and causes a corresponding or relative advancement ofplunger 62 toward syringe tip 64, thereby causing fluid to be expelledfrom syringe 60. Upward movement (or retraction) of drive member 79causes the barrel of syringe 60 to move upward and corresponds toretraction of plunger 62 relative to syringe tip 64, thereby drawingfluid into syringe 60.

[0071] An extending syringe adapter, such as adapter 400, enables use ofcommercially available injector systems and commercially available dosecalibrators in the system of the present invention without substantialmodification. The use of adapter 400 is transparent to the injectorcontrol software/hardware as no change and/or recalibration of thecontrolled movement of drive member 79 of injector 70 is required.

[0072]FIGS. 5A through 5D illustrate several other embodiments of thepresent invention for providing dose calibration generally in real time.In FIG. 5A, a pressurizing device 520 (for example, a syringe incommunication with a powered injector) and a radiopharmaceutical source540 are positioned within a dose calibrator 550. In FIG. 5B,radiopharmaceutical source 540 is placed in a dose calibrator 550′,while pressurizing device 520 is placed in a shielded enclosure 560. Inthe embodiment of FIGS. 5C and 5D, radiation level detectors are placedin operative connection with flow lines (for example, tubing). In FIG.5C, a radiation detector 570 is placed in line betweenradiopharmaceutical source 540 (enclosed within a shielded container580) and pressurizing device 520 (enclosed within a shielded container590). In FIG. 5D, a radiation detector 570′ is placed in line with theexit of pressurizing device 520. In general, the flow rate through theline in operative connection with radiation detector 570 or 570′ isknown. The radiation level of a particular dose is thus easily measuredusing radiation detectors 570 and/or 570′.

[0073] Although the present invention has been described in detail inconnection with the above examples, it is to be understood that suchdetail is solely for that purpose and that variations can be made bythose skilled in the art without departing from the spirit of theinvention except as it may be limited by the following claims.

What is claimed is:
 1. A method of injecting a hazardous pharmaceutical,said method comprising the steps of: (a) connecting a source of flushingfluid to a first port of a fluid delivery set; (b) connecting apressurizing unit of a powered injector system to a second port of thefluid delivery set, the powered injector system including a poweredinjector and the pressurizing unit; (c) purging air from the fluiddelivery set; and (d) after purging air from the fluid delivery set,connecting a third port of the fluid delivery set to a source of thehazardous pharmaceutical.
 2. The method of claim 1 wherein the fluiddelivery set includes a valve system to control flow of fluid throughthe fluid delivery set.
 3. The method of claim 1 wherein furtherincluding the steps of removably connecting a disposable fluid pathadapted to connect to a patient to the fluid delivery set and purgingair from the disposable fluid path before connecting the fluid deliveryset to the source of hazardous pharmaceutical.
 4. The method of claim 3wherein the pressurizing unit is a syringe in operative connection withthe powered injector, the method further including the steps of drawinghazardous pharmaceutical into the syringe and injecting the hazardouspharmaceutical through the fluid delivery set and the disposable fluidpath.
 5. The method of claim 4 further including the step of flushingthe fluid delivery set and the disposable fluid path after injectionusing the flushing fluid.
 6. The method of claim 4 wherein the hazardouspharmaceutical is a radiopharmaceutical, the method further includingthe step of measuring the level of radioactivity of theradiopharmaceutical dispensed.
 7. The method of claim 6 wherein thelevel of radioactivity is measured by positioning a radioactivitydetector in operative proximity to the syringe.
 8. The method of claim 6wherein the level of radioactivity is measured by placing aradioactivity detector in operative connection with a line through whichthe radiopharmaceutical is dispensed.
 9. A system for delivery of ahazardous pharmaceutical, said system comprising: (a) a syringe inoperative connection with a powered injector; (b) a protective containerto enclose the syringe during operation thereof, the protectivecontainer being adapted to protect personnel from detrimental effects ofthe pharmaceutical; (c) at least one source of flushing fluid; (d) afluid path adapted to connect to a patient; (e) at least one source ofthe pharmaceutical; and (f) a fluid delivery set including a valveassembly to which the syringe, the source of flushing fluid, the fluidpath and the source of pharmaceutical are removably connectable, thevalve assembly providing flow control through the fluid delivery setsuch that operator contact with the fluid delivery set is not requiredafter connection of the source of pharmaceutical to the fluid deliveryset.
 10. The system of claim 9 wherein valve assembly provides flowcontrol through the fluid delivery set such that the entire fluiddelivery set can be purged of air with the syringe and the source offlushing fluid in fluid connection with the valve assembly before thesource of pharmaceutical is connected to the fluid delivery set.
 11. Thesystem of claim 10 wherein the valve assembly includes a bypass line incontinuous fluid connection between the source of flushing fluid and thefluid path.
 12. The system of claim 9 wherein the pharmaceutical is aradiopharmaceutical and the protective container is in operativeproximity to a radioactivity detector adapted to measure the level ofradioactivity of the pharmaceutical within the syringe.
 13. The systemof claim 12 wherein the syringe is connected to the powered injector viaan extending adapter.
 14. The system of claim 13 wherein the adapterincludes an injector attachment member to attach the adapter to apowered injector, a plunger extension fixed in position relative to apowered injector and having a plunger attachment member to attach to aplunger of the syringe, a syringe carriage slidably attached to theadapter, the syringe carriage including a syringe attachment member toremovably attach a syringe thereto so that a barrel of a syringe can bemoved relative to a plunger thereof to control fluid flow into and outof a syringe.
 15. The adapter of claim 14 wherein a syringe is orientedwith a syringe tip thereof directed toward the powered injector when thesyringe is attached to the syringe attachment member.
 16. An adapter foruse with a powered injector to attach a syringe to the powered injector,said adapter comprising: (a) an injector attachment member to attach theadapter to the powered injector; and (b) a syringe attachment memberspaced from the injector attachment member by a sufficient distance toposition the syringe attached to the syringe attachment member inoperative proximity to a radioactivity detector, the syringe beingoriented with a tip thereof directed toward the powered injector whenattached to the syringe attachment member.
 17. An adapter for use with apowered injector to attach a syringe to the powered injector, saidadapter comprising: (a) an injector attachment member to attach theadapter to the powered injector; (b) a plunger extension fixed inposition relative to the powered injector and having a plungerattachment member to attach to a plunger of the syringe; and (c) asyringe carriage slidably attached to the adapter, the syringe carriageincluding a syringe attachment member to removably attach the syringethereto so that a barrel of the syringe can be moved relative to theplunger thereof to control fluid flow into and out of the syringe. 18.The adapter of claim 17 wherein a syringe is oriented with a syringe tipthereof directed toward the powered injector when attached to thesyringe attachment member.
 19. An adapter for use with a poweredinjector to attach a syringe to the powered injector comprising: anattachment member to removably attach the adapter to a powered injector,a syringe carriage slidably attached to the attachment member, thesyringe carriage including a syringe attachment member to which asyringe can be removably attached, the adapter further including an endmember attached a fixed distance from the attachment member, the endmember having a plunger extension attached to the end member andextending toward the injector, the plunger extension including a plungerattachment member on an end thereof opposite the end attached to the endmember, the syringe carriage adapted to move a barrel of the syringerelative to a plunger of the syringe when a syringe is attached to thesyringe attachment member and a plunger thereof is attached to theplunger extension member.
 20. A shield for use with aradiopharmaceutical, the shield including a housing that is impenetrableby radioactive energy from the radiopharmaceutical, the shield alsoincluding at least one opening in the housing through which an articlecontaining the radiopharmaceutical and positioned within the housing canbe viewed, the opening being in visual alignment with a reflectivesurface in which a viewer can view a reflection of the article, theopening being positioned within the housing such that there is no directline between the viewer and the article that is not shielded by aportion of the housing.
 21. A method of injecting a radiopharmaceuticalinto a body, said method including the steps of: (a) positioning apressurizing device containing a first volume of the radiopharmaceuticalwithin a dose calibrating unit adapted to measure the level ofradioactivity of the radiopharmaceutical; and (b) injecting a secondvolume of the radiopharmaceutical, the second volume being determinedthrough measurement by the dose calibrating unit to provide a desiredlevel of radioactivity.
 22. The method of claim 21 wherein the secondvolume is less than the first volume.
 23. The method of claim 21 whereinthe pressurizing device is a syringe in fluid connection with a poweredinjector.
 24. A kit for injecting a hazardous pharmaceutical into abody, said kit including: (a) a fluid path adapted to connect to apatient; and (b) a fluid delivery set, the fluid delivery set includinga valve assembly to which a pressurizing unit, a source of flushingfluid, the fluid path and a source of the pharmaceutical are removablyconnectable, the valve assembly providing flow control through the fluiddelivery set such that operator contact with the fluid delivery set isnot required after connection of the source of pharmaceutical to thefluid delivery set.
 25. The kit of claim 24 wherein the valve assemblyprovides flow control through the fluid delivery set such that theentire fluid delivery set can be purged of air with the syringe and thesource of saline in fluid connection with the valve assembly before thesource of pharmaceutical is connected to the fluid delivery set.
 26. Amethod of injecting a radiopharmaceutical into a patient, said methodcomprising the steps of: (a) connecting a powered pressurizing devicethat is controlled without close operator contact to a valve assembly ofa fluid delivery set; (b) connecting at least one source of a flushingfluid to the valve assembly; (c) connecting a patient fluid path to thevalve assembly, the patient fluid path terminating in a patientconnector; (d) connecting a ready-made source of the radiopharmaceuticalto the valve assembly; and (e) controlling the valve assembly at leastduring injection of the hazardous pharmaceutical such that operatorpresence in the vicinity of the radiopharmaceutical is not required. 27.The method of claim 26 further including the step of purging all linesof the fluid delivery set of air before connecting the source ofradiopharmaceutical to the valve assembly.
 28. The method of claim 26further including the step of shielding at least a portion of thepressurizing device that contacts the radiopharmaceutical.
 29. Themethod of claim 26 further including the step of shielding at least aportion of the fluid delivery set.
 30. The method of claim 26 furtherincluding the step of measuring the radioactivity of a dose ofradiopharmaceutical delivered to the patient generally simultaneouslywith injecting the radiopharmaceutical.
 31. The method of claim 26wherein the valve assembly is controlled without close operator contact.